The asymmetric coupling reaction of aldehydes and alkynes is known. In particular, the preparation of chiral propargyl alcohols, such as 3-hydroxy-1-butyne, using zinc triflate in an enantioselective aldehyde addition reaction with a terminal alkyne, in the presence of triethylamine and (+)- or (−)-N-methylephedrine has been described. (See for example, Carreira et al, Organic Letters, 2000, 2(26), 4233-4236 and Carreira et al, J. Am. Chem. Soc., 2000, 122, 1806-1807). By the term ‘terminal’ we mean an alkyne having a hydrogen atom bound to one carbon atom forming the carbon-carbon triple bond, i.e. a C≡C—H group. This reaction has been used to provide chiral propargyl alcohols, via, for example, thermally unstable alkynediols. However these workers have only considered aldehydes having 3 or more carbon atoms. Similarly, WO 02/094741 describes a process for performing coupling reactions to prepare 1,4-, 1,5- or 1,6- diols from aldehydes and hydroxyalkynes wherein the aldehydes are of general formula R1C(O)H in which R1 represents a saturated or unsaturated alkyl having between 2 and 24 carbon atoms, cycloalkyl or aryl group.
Acetaldehyde (CH3CHO) has presented practical challenges that have prevented its successful use in Lewis acid mediated coupling reactions such as those described above. In particular, the propensity of acetaldehyde for self-condensation to form mixed oligomeric species has presented a significant obstacle. Consequently, useful acetaldehyde-derived products such as chiral alkynes and chiral 1,4-diols and their derivatives have not been successfully obtained in commercially attractive yields.